INDUCTION: The interaction of the virus genome with the host cell genome in transformed cells is being investigated. Specifically, analyses will be made of the early events in induction utilizing chemicals and radiation. The mechanism of viral derepression and excision of the viral genome, in particular the effects of breaks in the host cell DNA, on virus induction will be examined. The properties of excised viral DNA, the kinetics of virus DNA synthesis, viral transcription, and the factors involved in permissivity will be probed by comparing induction in various clones of transformed hamster cells which are heterogeneous with respect to their inducibility. CELL SURFACE: The mechanism(s) responsible for the phenotype of the transformed cell will be analyzed with emphasis on the role of cellular proteases. The process regulating secretion will be studied since continuous secretion of proteases occurs from transformed cells while secretion of proteases, which occurs in normal growing cells, ceases in normal confluent cells. A relationship between secretion of cellular proteases and loss of proteins from the transformed cell surface will be sought. ANTIBODY PRODUCING TRANSFORMED CELL LINES: Studies whereby antibody producing rabbit lymphoreticular cells have been transformed by SV40 and Herpesvirus saimiri and converted to antibody secreting autonomous cell lines will be continued. We plan to produce an autonomous human lymphoreticular cell line secreting antibody which could be utilized for diagnosis and therapy of human diseases by sensitizing human lymphoid cells against a relevant antigen such as digoxin and subsequently transforming these cells with a B lymphocyte tropic virus such as EBV.